In Salmonella typhimurium, inorganic sulfate undergoes assimilatory reduction to sulfide, which in turn reacts with O-acetylserine to form L-cysteine. This cysteine biosynthetic pathway is controlled by a combination of feedback inhibition and a system of positive gene control in which O-acetylserine itself is an internal inducer. We shall attempt to isolate and characterize the cysB gene product, which is a protein necessary for the expression of the cysteine biosynthetic pathway. Cystine transport is also regulated by cysB and O-acetylserine; mutants in this activity will be isolated and genetically mapped. Mammalian cells complete the sulfur cycle by degrading methionine and cysteine to inorganic sulfate and several other highly oxidized formed of sulfur. We shall attempt to identify mammalian cell lines in which sulfur catabolism is active. By nutritional and enzymatic studies, we hope to elucidate those factors which regulate the flow of sulfur through these pathways. An important aim of these studies is to identify appropriate cell strains and to develop biochemical techniques for isolating and studying mutant mammalian cells which are defective in the control of sulfur catabolism.